Peter Mariën

Consensus paper: roles of the cerebellum in motor control--the diversity of ideas on cerebellar involvement in movement.

Considerable progress has been made in developing models of cerebellar function in sensorimotor control, as well as in identifying key problems that are the focus of current investigation. In this consensus paper, we discuss the literature on the role of the cerebellar circuitry in motor control, bringing together a range of different viewpoints. The following topics are covered: oculomotor control, classical conditioning (evidence in animals and in humans), cerebellar control of motor speech, control of grip forces, control of voluntary limb movements, timing, sensorimotor synchronization, control of corticomotor excitability, control of movement-related sensory data acquisition, cerebro-cerebellar interaction in visuokinesthetic perception of hand movement, functional neuroimaging studies, and magnetoencephalographic mapping of cortico-cerebellar dynamics. While the field has yet to reach a consensus on the precise role played by the cerebellum in movement control, the literature has witnessed the emergence of broad proposals that address cerebellar function at multiple levels of analysis. This paper highlights the diversity of current opinion, providing a framework for debate and discussion on the role of this quintessential vertebrate structure.

Cerebellar neurocognition: insights into the bottom of the brain

The traditional view on the core functions of the cerebellum consists of the regulation of motor coordination, balance and motor speech. However, during the past decades results from neuroanatomical, neuroimaging and clinical studies have substantially extended the functional role of the cerebellum to cognitive and affective regulation. Neuroanatomical studies convincingly showed cerebellar connectivity with associative areas of the cerebral cortex involved in higher cognitive functioning, while functional neuroimaging provided evidence of cerebellar activation during a variety of cognitive tasks. In addition, more systematic neuropsychological research performed in patients with cerebellar lesions and the development of more sensitive neuropsychological tests allowed clinicians to identify significant cognitive and affective disturbances following cerebellar damage. In this review, an overview is presented of the cerebellar role in a variety of cognitive processes, such as executive functioning, memory, learning, attention, visuo-spatial regulation, language and behavioral-affective modulation. In addition, recent evidence with regard to cerebellar induced clinical entities such as the cerebellar cognitive affective syndrome (CCAS) and the posterior fossa syndrome (PFS), will be discussed. Although extensive research has substantially broadened the insights in the cognitive and affective role of the cerebellum, the precise nature of the cerebellar contribution to cognitive and affective regulation is not yet clear. In this review experimental and clinical data will be discussed that substantiate the presumed neurobiological mechanisms underlying the cognitive and affective modulatory role of the cerebellum.

Consensus Paper: Language and the Cerebellum: an Ongoing Enigma

In less than three decades, the concept “cerebellar neurocognition” has evolved from a mere afterthought to an entirely new and multifaceted area of neuroscientific research. A close interplay between three main strands of contemporary neuroscience induced a substantial modification of the traditional view of the cerebellum as a mere coordinator of autonomic and somatic motor functions. Indeed, the wealth of current evidence derived from detailed neuroanatomical investigations, functional neuroimaging studies with healthy subjects and patients and in-depth neuropsychological assessment of patients with cerebellar disorders shows that the cerebellum has a cardinal role to play in affective regulation, cognitive processing, and linguistic function. Although considerable progress has been made in models of cerebellar function, controversy remains regarding the exact role of the “linguistic cerebellum” in a broad variety of nonmotor language processes. This consensus paper brings together a range of different viewpoints and opinions regarding the contribution of the cerebellum to language function. Recent developments and insights in the nonmotor modulatory role of the cerebellum in language and some related disorders will be discussed. The role of the cerebellum in speech and language perception, in motor speech planning including apraxia of speech, in verbal working memory, in phonological and semantic verbal fluency, in syntax processing, in the dynamics of language production, in reading and in writing will be addressed. In addition, the functional topography of the linguistic cerebellum and the contribution of the deep nuclei to linguistic function will be briefly discussed. As such, a framework for debate and discussion will be offered in this consensus paper.

The cerebellum: Its role in language and related cognitive and affective functions

The traditional view on the cerebellum as the sole coordinator of motor function has been substantially redefined during the past decades. Neuroanatomical, neuroimaging and clinical studies have extended the role of the cerebellum to the modulation of cognitive and affective processing. Neuroanatomical studies have demonstrated cerebellar connectivity with the supratentorial association areas involved in higher cognitive and affective functioning, while functional neuroimaging and clinical studies have provided evidence of cerebellar involvement in a variety of cognitive and affective tasks. This paper reviews the recently acknowledged role of the cerebellum in linguistic and related cognitive and behavioral-affective functions. In addition, typical cerebellar syndromes such as the cerebellar cognitive affective syndrome (CCAS) and the posterior fossa syndrome (PFS) will be briefly discussed and the current hypotheses dealing with the presumed neurobiological mechanisms underlying the linguistic, cognitive and affective modulatory role of the cerebellum will be reviewed.

Social cognition and the cerebellum: a meta-analysis of over 350 fMRI studies.

This meta-analysis explores the role of the cerebellum in social cognition. Recent meta-analyses of neuroimaging studies since 2008 demonstrate that the cerebellum is only marginally involved in social cognition and emotionality, with a few meta-analyses pointing to an involvement of at most 54% of the individual studies. In this study, novel meta-analyses of over 350 fMRI studies, dividing up the domain of social cognition in homogeneous subdomains, confirmed this low involvement of the cerebellum in conditions that trigger the mirror network (e.g., when familiar movements of body parts are observed) and the mentalizing network (when no moving body parts or unfamiliar movements are present). There is, however, one set of mentalizing conditions that strongly involve the cerebellum in 50-100% of the individual studies. In particular, when the level of abstraction is high, such as when behaviors are described in terms of traits or permanent characteristics, in terms of groups rather than individuals, in terms of the past (episodic autobiographic memory) or the future rather than the present, or in terms of hypothetical events that may happen. An activation likelihood estimation (ALE) meta-analysis conducted in this study reveals that the cerebellum is critically implicated in social cognition and that the areas of the cerebellum which are consistently involved in social cognitive processes show extensive overlap with the areas involved in sensorimotor (during mirror and self-judgments tasks) as well as in executive functioning (across all tasks). We discuss the role of the cerebellum in social cognition in general and in higher abstraction mentalizing in particular. We also point out a number of methodological limitations of some available studies on the social brain that hamper the detection of cerebellar activity.

Cognitive and affective disturbances following focal cerebellar damage in adults: a neuropsychological and SPECT study

The traditional view on cerebellar functioning has recently been challenged by results from neuroanatomical, neuroimaging and clinical studies. In this contribution, eighteen patients with primary cerebellar lesions (vascular: n=13; neoplastic: n=5) were systematically investigated by means of an extensive neuropsychological test battery. Fifteen patients (83%) presented with a broad variety of cognitive and linguistic deficits following cerebellar damage. Disturbances of attention (72%), executive functioning (50%) and memory (50%) were most commonly found. Analyses of our results tend to support the hypothesis of a lateralization of cognitive modulation within the cerebellum, the right cerebellar hemisphere being associated with logical reasoning and language processing and the left cerebellum mediating right-hemispheric functions including attentional and visuo-spatial skills. In addition, nine patients (50%) presented with frontal-like behavioural and affective alterations. In an attempt to determine the working-mechanism underlying cerebellar-induced cognitive and affective disturbances, all patients were investigated by means of quantified Tc-99m-ethylenecysteine dimer (ECD) single photon emission computerized tomography (SPECT) studies. From a semiological point of view, damage to the cerebellum can cause a broad spectrum of clinically significant cognitive and affective disturbances. From a pathophysiological point of view, quantified SPECT data, reflecting the phenomenon of cerebello-cerebral diaschisis, support the functional impact of the cerebellar lesion on cortical functioning through disruption of cerebello-cerebral connections.

Cognitive, linguistic and affective disturbances following a right superior cerebellar artery infarction: A case study

The cerebellar cognitive affective syndrome (CCAS) is a neurobehavioral syndrome that may develop after congenital and acquired cerebellar lesions. The syndrome consists of deficits in executive functioning, spatial cognition, visual-spatial memory and language and also involves personality and behavioral changes. We describe a 58-year-old right-handed man who in addition to affective disturbances presented with a unique combination of cognitive and linguistic deficits following an ischemic infarction in the vascular territory of the right superior cerebellar artery (SCA). Neurocognitive and neurolinguistic examinations were performed in the acute phase (10 days post-onset) and lesion phase (four weeks post-onset) of the stroke. A Tc-99m-ECD SPECT study was performed five weeks after the stroke. Acute phase data revealed a generalized cognitive decline and mild transcortical sensory aphasia. In the lesion phase, the neurobehavioral tableau was dominated by executive dysfunctions, disrupted divided attention, disturbed visual-spatial organization and behavioral abnormalities. Neurolinguistic investigations disclosed visual dyslexia and surface dysgraphia. Reading of words and visual lexical decision tasks of words and nonwords were severely defective and predominantly characterized by visual errors. In addition, writing irregular and ambiguous words resulted in regularization errors (phonologically plausible errors based on phoneme-grapheme correspondence rules). In the absence of any structural damage in the supratentorial brain regions, a quantified SPECT study showed a relative hypoperfusion in the right cerebellar hemisphere and the left medial frontal lobe. CCAS is for the first time reported in association with visual dyslexia and surface dysgraphia. We hypothesize that the cognitive and linguistic deficits might result from functional disruption of the cerebellar-encephalic pathways, connecting the cerebellum to the frontal supratentorial areas which subserve attentional and planning processes. This phenomenon of crossed cerebellar-cerebral diaschisis is supported by SPECT findings revealing a hypoperfusion in the anatomoclinically suspected brain regions. The constellation of cognitive, linguistic and behavioral symptoms adds new evidence to the multifaceted area of cerebellar neurocognition and demonstrates that the cerebellum might play a crucial role in cognitive, linguistic, and affective processing.

Consensus Paper: Revisiting the Symptoms and Signs of Cerebellar Syndrome

The cerebellum is involved in sensorimotor operations, cognitive tasks and affective processes. Here, we revisit the concept of the cerebellar syndrome in the light of recent advances in our understanding of cerebellar operations. The key symptoms and signs of cerebellar dysfunction, often grouped under the generic term of ataxia, are discussed. Vertigo, dizziness, and imbalance are associated with lesions of the vestibulo-cerebellar, vestibulo-spinal, or cerebellar ocular motor systems. The cerebellum plays a major role in the online to long-term control of eye movements (control of calibration, reduction of eye instability, maintenance of ocular alignment). Ocular instability, nystagmus, saccadic intrusions, impaired smooth pursuit, impaired vestibulo-ocular reflex (VOR), and ocular misalignment are at the core of oculomotor cerebellar deficits. As a motor speech disorder, ataxic dysarthria is highly suggestive of cerebellar pathology. Regarding motor control of limbs, hypotonia, a- or dysdiadochokinesia, dysmetria, grasping deficits and various tremor phenomenologies are observed in cerebellar disorders to varying degrees. There is clear evidence that the cerebellum participates in force perception and proprioceptive sense during active movements. Gait is staggering with a wide base, and tandem gait is very often impaired in cerebellar disorders. In terms of cognitive and affective operations, impairments are found in executive functions, visual-spatial processing, linguistic function, and affective regulation (Schmahmann’s syndrome). Nonmotor linguistic deficits including disruption of articulatory and graphomotor planning, language dynamics, verbal fluency, phonological, and semantic word retrieval, expressive and receptive syntax, and various aspects of reading and writing may be impaired after cerebellar damage. The cerebellum is organized into (a) a primary sensorimotor region in the anterior lobe and adjacent part of lobule VI, (b) a second sensorimotor region in lobule VIII, and (c) cognitive and limbic regions located in the posterior lobe (lobule VI, lobule VIIA which includes crus I and crus II, and lobule VIIB). The limbic cerebellum is mainly represented in the posterior vermis. The cortico-ponto-cerebellar and cerebello-thalamo-cortical loops establish close functional connections between the cerebellum and the supratentorial motor, paralimbic and association cortices, and cerebellar symptoms are associated with a disruption of these loops.

Pathophysiology of language switching and mixing in an early bilingual child with subcortical aphasia

Acquired aphasia after circumscribed vascular subcortical lesions has not been reported in bilingual children. We report clinical and neuroimaging findings in an early bilingual boy who incurred equally severe transcortical sensory aphasia in his first language (L1) and second language (L2) after a posterior left thalamic hemorrhage. Following recurrent bleeding of the lesion the aphasic symptoms substantially aggravated. Spontaneous pathological language switching and mixing were found in both languages. Remission of these phenomena was reflected on brain perfusion SPECT revealing improved perfusion in the left frontal lobe and left caudate nucleus. The parallelism between the evolution of language symptoms and the SPECT findings may demonstrate that a subcortical left frontal lobe circuity is crucially involved in language switching and mixing.

Loss of Psychic Self-Activation After Paramedian Bithalamic Infarction

BACKGROUND AND PURPOSE Loss of psychic self-activation has been described after bilateral lesions to the globus pallidus, striatum, and white matter of the frontal lobes, but it is a very rare sign of bithalamic lesions. The exact functional-anatomic mechanism underlying loss of psychic self-activation following bithalamic lesions remains to be elucidated. CASE DESCRIPTION We present clinical, neuropsychological, structural, and functional neuroimaging data of an 18-month follow-up period of a man with prominent loss of psychic self-activation after coronary arteriography. Except for memory decline, accompanying symptoms remained restricted to the acute phase. The neurobehavioral syndrome consisted mainly of apathy, indifference, poor motivation, and flattened affect, and this remained unchanged during the entire follow-up period. MRI showed a bithalamic infarction involving the nucleus medialis thalami bilaterally. Single-photon emission CT revealed a severe relative hypoperfusion of both thalami, a relative hypoperfusion of both nuclei caudati, and a relative hypoperfusion mesiofrontally. CONCLUSIONS Single-photon emission CT data support the hypothesis that the neurobehavioral manifestations after bithalamic paramedian infarction are caused by disruption of the striatal-ventral pallidal-thalamic-frontomesial limbic loop. Probably, bilateral disruption at different levels of the striatal-ventral pallidal-thalamic-frontomesial loop may lead to a similar clinical picture consisting of loss of psychic self-activation.